Induction of secondary metabolism of Aspergillus terreus ATCC 20542 in the batch bioreactor cultures

• Published in: Applied microbiology and biotechnology Vol. 100; no. 7; pp. 3009 - 3022
• Main Authors: Boruta, Tomasz, Bizukojc, Marcin
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2016; Springer; Springer Nature B.V
• Subjects: 4-Butyrolactone - analogs & derivatives; 4-Butyrolactone - biosynthesis; Acids; Aeration; Anthraquinones - metabolism; Aspergillus; Aspergillus - drug effects; Aspergillus - metabolism; Bacterial cultures; Batch Cell Culture Techniques; Benzofurans - metabolism; Biomass; Biomedical and Life Sciences; Bioreactors; Biosynthesis; Biotechnological Products and Process Engineering; Biotechnology; Chlorine; Chromatography, High Pressure Liquid; Cultivation; Cyclopentanes - metabolism; Fatty Acids, Monounsaturated - metabolism; Fatty Acids, Monounsaturated - pharmacology; Fermentation; Fungi; Genetic engineering; Growth media; Inulin - metabolism; Inulin - pharmacology; Life Sciences; Liquid chromatography; Lovastatin - analogs & derivatives; Lovastatin - biosynthesis; Mass spectra; Mass spectrometry; Membrane reactors; Metabolism; Metabolites; Microbial Genetics and Genomics; Microbiology; Nitrogen; Observations; Phenyl Ethers - metabolism; Physiological aspects; Pyridones - metabolism; Rapeseed Oil; Secondary Metabolism - drug effects; Secondary metabolites; Studies; Poland; Lovastatin; Secondary metabolites; (+)-Geodin; Aspergillus terreus
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/s00253-015-7157-1

Cultivation of Aspergillus terreus ATCC 20542 in a stirred tank bioreactor was performed to induce the biosynthesis of secondary metabolites and provide the bioprocess-related insights into the metabolic capabilities of the investigated strain. The activation of biosynthetic routes was attempted by the diversification of process conditions and growth media. Several strategies were tested, including the addition of rapeseed oil or inulin, changing the concentration of nitrogen source, reduction of chlorine supply, cultivation under saline conditions, and using various aeration schemes. Fifteen secondary metabolites were identified in the course of the study by using ultra-high performance liquid chromatography coupled with mass spectrometry, namely mevinolinic acid, 4a,5-dihydromevinolinic acid, 3α-hydroxy-3,5-dihydromonacolin L acid, terrein, aspulvinone E, dihydroisoflavipucine, (+)-geodin, (+)-bisdechlorogeodin, (+)-erdin, asterric acid, butyrolactone I, desmethylsulochrin, questin, sulochrin, and demethylasterric acid. The study also presents the collection of mass spectra that can serve as a resource for future experiments. The growth in a salt-rich environment turned out to be strongly inhibitory for secondary metabolism and the formation of dense and compact pellets was observed. Generally, the addition of inulin, reducing the oxygen supply, and increasing the content of nitrogen source did not enhance the production of examined molecules. The most successful strategy involved the addition of rapeseed oil to the chlorine-deficient medium. Under these conditions, the highest levels of butyrolactone I, asterric acid, and mevinolinic acid were achieved and the presence of desmethylsulochrin and (+)-bisdechlorogeodin was detected in the broth. The constant and relatively high aeration rate in the idiophase was shown to be beneficial for terrein and (+)-geodin biosynthesis.